Dimethylformamide → HCID 86719402, compound

HRID 2175664Notes

Reaction equation

HRID 2175664 reaction equation
Br[C:2]1[N:18]([C@@H:19]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20]2)[C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:4]=2[C:3]=1[C:31]1[CH:36]=[CH:35][C:34]([O:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[CH:33][CH:32]=1.[Li]CCCC.CN([CH:52]=[O:53])C>C1COCC1>[C:14]([O:13][C:11]([NH:10][C:9]1[C:4]2[C:3]([C:31]3[CH:36]=[CH:35][C:34]([O:37][C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)=[CH:33][CH:32]=3)=[C:2]([CH:52]=[O:53])[N:18]([C@@H:19]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:20]3)[C:5]=2[N:6]=[CH:7][N:8]=1)=[O:12])([CH3:16])([CH3:15])[CH3:17]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 86719403HCID 86719403, compoundHCID 178418339Butyllithium

Product 1

HCID 86719402HCID 86719402, compoundYield 8.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

At −78° C. under N2 atmosphere, to a solution of (R)-tert-butyl 3-(6-bromo-4-(tert-butoxycarbonylamino)-5-(4-phen-oxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (119) (1.57 g, 2.41 mmol) in THF (20 mL) was added n-BuLi (3 mL, 7.23 mmol, 2.5M in THF) dropwise. The resulting mixture was stirred at −78° C. for 1 hr before introducing DMF (264 mg, 3.62 mmol). Stirring was continued for another 1 hr at −78° C. The reaction was quenched with sat. NH4Cl before extracted with EA (30 mL×3). Combined organic layers were washed with brine and dried over Na2SO4. Solvents were removed under vacuum and the residue was purified by flash chromatography (silica gel, 0 to 50% EA in PE) to provide (R)-tert-butyl 3-(4-(tert-butoxycarbonylamino)-6-formyl-5-(4-phenoxyphenyl)-7H-pyrr-olo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (120) (118 mg, 8%) as a yellow oil. LC-MS (ESI): m/z (M+1) 600.0.

Workup

  1. stirringStirring
  2. waitwas continued for another 1 hr at −78° C
  3. customThe reaction was quenched with sat. NH4Cl
  4. extractionbefore extracted with EA (30 mL×3)
  5. washCombined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. customSolvents were removed under vacuum
  8. customthe residue was purified by flash chromatography (silica gel, 0 to 50% EA in PE)

Sources & evidence

ORD record
ord-3c647a828c4b4398af72dc5d8e4804d0
Source dataset
uspto-grants-2015_06
Patent number
US09062058B2

Reaction notes

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